BOVINE ALPHA-S1-CASEIN GENE-SEQUENCES DIRECT HIGH-LEVEL EXPRESSION OF ACTIVE HUMAN UROKINASE IN MOUSE MILK

We have produced a line of transgenic mice carrying a hybrid bovine αs1 casein/human urokinase gene. Bovine αs1-casein gene regulatory sequences specifically direct expression of the human urokinase gene in lactating mammary tissue from these mice. Urokinase is a 54 kD protein with 9 disulfide bonds that is normally synthesized in the kidney; however, the casein/urokinase transgenic mice secrete active human urokinase into their milk at concentrations of 1-2 mg/ml. The mice show no other abnormalities. They give birth to, and nurse, normal sized healthy litters. Thus it is possible to produce high concentrations of a large, cysteine rich, non-milk protein in the milk of transgenic animals. This line of transgenic mice provides a model for the eventual production of transgenic farm animals producing high levels of recombinant proteins in their milk. © 1990 Nature Publishing Group.